Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan-Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16-2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79-1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression.

HLA markers in patients suffering from aplastic anaemia.

135 patients, suffering from aplastic anaemia (AA) and their families were genotyped for HLA. The antigen and haplotype frequencies were compared to an HLA genotyped control panel composed of 209 normal couples and their healthy offsprings, and to another series of 2286 normal individuals. An excess of HLA-A2 was observed in the patients: 61% versus 42% (pc less than 0.001) (relative risk: 2) and versus 48.5% (p less than 0.01) in two control series, respectively. When considering the HLA-A, B antigens shared in common by the parents of the AA patients, an excess of HLA-A2 was observed: 32% as compared to 17% shared by normal couples (p less than 0.001). An excess of homozygous HLA-A2 was noted in the AA patients (14%) in comparison to the normal controls (4%) (p less than 0.001). The mechanism of this association is discussed as well as the hypothesis of a gene involved in haematopoiesis which might interact within the HLA-A region.